(5-Amino-2-fluoro-phenyl)-(1-methyl-piperidin-4-yl)-methanone | 823191-41-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (5-Amino-2-fluoro-phenyl)-(1-methyl-piperidin-4-yl)-methanone
• 英文别名: (5-Amino-2-fluorophenyl)(1-methylpiperidin-4-yl)methanone；(5-amino-2-fluorophenyl)-(1-methylpiperidin-4-yl)methanone
• CAS: 823191-41-9
• 化学式: C₁₃H₁₇FN₂O
• 分子量: 236.289
• InChiKey: HAFJVPROJMEOIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5-Amino-2-fluoro-phenyl)-(1-methyl-piperidin-4-yl)-methanone 在 吡啶 、 sodium hydroxide 、 盐酸羟胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 生成 3-(1-Methyl-piperidin-4-yl)-benzo[d]isoxazol-5-ylamine
  参考文献：
  名称：

  Design, synthesis and evaluation of bicyclic benzamides as novel 5-HT1F receptor agonists

  摘要：

  Several fused bicyclic systems have been investigated to serve as the core structure of potent and selective 5-HT1F receptor agonists. Replacement of the indole nucleus in 2 with indazole and 'inverted' indazole provided more potent and selective 5-HT1F receptor ligands. Indoline and 1,2-benzisoxazole systems also provided potent 5-HT1F receptor agonists, and the 5-HT1A receptor selectivity of the indoline- and 1,2-benzisoxazole-based 5-HT1F receptor agonists could be improved with modification of the benzoyl moiety of the benzamides. Through these studies, we found that the inherent geometries of the templates, not the nature of hybridization of the linking atom, were important for the 5-HT1F receptor recognition. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.09.079
• 作为产物：
  描述：

  N-甲氧基-N,1-二甲基哌啶-4-羧酰胺 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 正丁基锂 、 四甲基乙二胺 、 水 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 (5-Amino-2-fluoro-phenyl)-(1-methyl-piperidin-4-yl)-methanone
  参考文献：
  名称：

  基于选择性N- [3-（1-甲基-哌啶-4-羰基）-苯基]-苯甲酰胺的5-HT 1F受体激动剂的发现：从双环核到单环核的演变

  摘要：

  临床前实验和临床观察表明，偏头痛中选择性5-HT 1F受体激动剂的潜在有效性。鉴定具有增强选择性的化合物对于评估其治疗价值至关重要。在吲哚核的代用2（LY334370）与单环苯基酮部分产生有效的和更具选择性的5-HT 1F受体激动剂。围绕该中心苯环的SAR研究重点表明，取代基与酰胺CONH基团和酮C O基团的静电和空间相互作用在影响所采用的构象中起着关键作用，因此影响了5-HT 1F受体选择性。计算研究证实了观察到的结果，并为理解5-HT 1F受体激动剂活性和选择性的构象要求提供了有用的工具。通过这种努力，还确定了2-F-苯基和N -2-吡啶基系列是有效的和选择性的5-HT 1F受体激动剂。

  DOI：

  10.1016/j.bmcl.2015.07.042

文献信息

• Discovery of selective N-[3-(1-methyl-piperidine-4-carbonyl)-phenyl]-benzamide-based 5-HT1F receptor agonists: Evolution from bicyclic to monocyclic cores
  作者：Deyi Zhang、Maria-Jesus Blanco、Bai-Ping Ying、Daniel Kohlman、Sidney X. Liang、Frantz Victor、Qi Chen、Joseph Krushinski、Sandra A. Filla、Kevin J. Hudziak、Brian M. Mathes、Michael P. Cohen、DeAnna Zacherl、David L.G. Nelson、David B. Wainscott、Suzanne E. Nutter、Wendy H. Gough、John M. Schaus、Yao-Chang Xu

  DOI：10.1016/j.bmcl.2015.07.042

  日期：2015.10

  nucleus in 2 (LY334370) with a monocyclic phenyl ketone moiety generated potent and more selective 5-HT1F receptor agonists. Focused SAR studies around this central phenyl ring demonstrated that the electrostatic and steric interactions of the substituent with both the amide CONH group and the ketone CO group play pivotal roles in affecting the adopted conformation and thus the 5-HT1F receptor selectivity

  临床前实验和临床观察表明，偏头痛中选择性5-HT 1F受体激动剂的潜在有效性。鉴定具有增强选择性的化合物对于评估其治疗价值至关重要。在吲哚核的代用2（LY334370）与单环苯基酮部分产生有效的和更具选择性的5-HT 1F受体激动剂。围绕该中心苯环的SAR研究重点表明，取代基与酰胺CONH基团和酮C O基团的静电和空间相互作用在影响所采用的构象中起着关键作用，因此影响了5-HT 1F受体选择性。计算研究证实了观察到的结果，并为理解5-HT 1F受体激动剂活性和选择性的构象要求提供了有用的工具。通过这种努力，还确定了2-F-苯基和N -2-吡啶基系列是有效的和选择性的5-HT 1F受体激动剂。
• Design, synthesis and evaluation of bicyclic benzamides as novel 5-HT1F receptor agonists
  作者：Deyi Zhang、Dan Kohlman、Joseph Krushinski、Sidney Liang、Bai-Ping Ying、John E. Reilly、Sean R. Dinn、David B. Wainscott、Suzanne Nutter、Wendy Gough、David L.G. Nelson、John M. Schaus、Yao-Chang Xu

  DOI：10.1016/j.bmcl.2004.09.079

  日期：2004.12

  Several fused bicyclic systems have been investigated to serve as the core structure of potent and selective 5-HT1F receptor agonists. Replacement of the indole nucleus in 2 with indazole and 'inverted' indazole provided more potent and selective 5-HT1F receptor ligands. Indoline and 1,2-benzisoxazole systems also provided potent 5-HT1F receptor agonists, and the 5-HT1A receptor selectivity of the indoline- and 1,2-benzisoxazole-based 5-HT1F receptor agonists could be improved with modification of the benzoyl moiety of the benzamides. Through these studies, we found that the inherent geometries of the templates, not the nature of hybridization of the linking atom, were important for the 5-HT1F receptor recognition. (C) 2004 Elsevier Ltd. All rights reserved.